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1. Instituto de Biologia do Exército, Rio de Janeiro, RJ. 2. Faculdade de Medicina, Universidade Estadual do Amazonas, Manaus, AM. 3. Departamento Clínico, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, AM.
Address to: Dr. Iran Mendonça da Silva. Travessa Laguna 12. Lírio do Vale, 69038-010 Manaus, AM, Brasil.
Phone: 55 92 2127-3496; Fax: 55 92 2127-3462
e-mail: silva.iran@ig.com.br
Received in 07/12/2010
Accepted in 19/09/2011
Revista da Sociedade Brasileira de Medicina Tropical 45(4):523-525, Jul-Aug, 2012
Communication/Comunicação
Comparative evaluation of adverse efects in the use of powder trivalent
antivenom and liquid antivenoms in
Bothrops
snake bites
Avaliação comparativa de efeitos adversos no uso do soro antiofídico trivalente lioilizado
e soros antiofídicos líquidos no acidente botrópico
Iran Mendonça da Silva
1,2and Antônio Magela Tavares
3ABSTACT
Introduction: Snake bite, a problem in public health, generally occurs where there is no electric power. Methods: A comparative clinical study was conducted with 102 victims of Bothrops snake bite, from the State of Amazonas, Brazil; 58 victims were treated with lioilizated trivalent antivenom serum (SATL) and 44 victims treated with liquid bivalent and monovalent antivenom serum (SAMBL). Results: 17% (10/58) of patients presented adverse efects with the SATL and 25% (11/44) with the SAMBL. Conclusions: here was no statistic diference in number of adverse efects between the two types of snake bite antivenom.
Keywords:Bothrops. Antivenoms. Adverse efects.
RESUMO
Introdução: Acidente ofídico, problema de Saúde Pública, é mais frequente onde não há energia elétrica. Métodos: Foi realizado estudo clínico comparativo com 102 vítimas de acidente botrópico, do Estado do Amazonas, Brasil; 58 vítimas tratadas com soro antiofídico trivalente lioilizado (SATL) e 44 vítimas tratadas com soro antiofídico monovalente e bivalente líquido (SAMBL). Resultados:A comparação entre os tipos de soro demonstrou 17% (10/58) de indivíduos com eventos adversos com o uso de SATL e 25% (11/44) com o uso dos SAMBL. Conclusões: Não houve diferença estatística na quantidade de reações adversas entre os dois tipos de soros antiofídicos.
Palavras-chaves:Bothrops. Soro antiofídico. Efeitos adversos.
In Brazil, snake bite is a problem in public health1; generally,
it occurs where there is no electric power, far from hospitals, for example, in forests of the Amazon Region, in ield activities, and in communities of people of indigenous origin2-4, where this study was
conducted. he registers of the Brazilian Health Ministry list about 20,000 victims of snake bite per year in the Brazilian territory. his statistic number is not exact, as many snake bites occur where there is no health unit to handle the notiication. Many times, the victims allow the snake bites to naturally heal without antivenoms and in some cases with signiicant complications5-7. hey lose ingers, legs,
hands, and arms, and they cannot work as well as they could before the snake bite. hey have serious complications such as infections, kidney failure and death8. In these distant regions, because of the lack
of electric power, it is impossible to conserve the liquid antivenom in low temperature between 20C and 80C, as recommended.
his evaluation is a clinical study to verify the safety of the Brazilian powder trivalent antivenom compared with the Brazilian liquid antivenom, made by the Butantan Institute, in the State of São Paulo, Brazil and the Ezequiel Dias Foundation (Fundação Ezequiel Dias - FUNED) and Vital Brazil Institute (Instituto Vital Brasil - IVB). The powder trivalent antivenom was also made in the Butantan Institute in association with the Biological Institute of Brazilian Army, in Rio de Janeiro (Instituto de Biologia do Exército - IBEx). Thus, Butantan Institute handled the final industrial production and the IBEx performed the clinical study.
The SATL was produced by the Butantan Institute in association with the IBEx. A prospective study was realized to compare the adverse effects between two antivenoms. During the 6 years of comparative study, the powder antivenom was revalidated after analysis and emission of the Butantan Institute certification to perform the analysis without interruption. To be considered for inclusion in the project, the patients had to have only light to moderate snake bite damages. We considered that during this phase, the severe envenoming could be a variable to confuse the results. The participants in the study should not be pregnant and had to be between 12 and 70 years of age; this selection of age was to avoid the exclusion of victims in rural work5
and to exclude immunological vulnerability and others diseases commonly found outside this range (i.e., those previous snake bite treatments and who are free from allergic effects caused by horsehairs and other horse proteins). In the case of the victims of the Bothrops snake bite, the participants to be treated with liquid or powered antivenom were chosen randomly after diagnosis of envenoming, after explanation about the project and after signing the informed consent form. The clinical experiment was considered a simple blind study, that is, only the health workers knew which antivenom was being used. The patients were not informed; they knew only that they were participating in a project comparing two kinds of antivenom. he protocol of this study was approved by the Research Ethics Commitee of the Army Biology Institute (Instituto de Biologia do Exército), Rio de Janeiro, and it was sent to National Ethical Commitee. he guidelines for human experimentation of the National Health Council were followed in the conduct of clinical research. he Pearsons χ2 test was used to
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Silva IM and Tavares AM - Adverse efects of powder and liquid antivenoms in Bothrops snake bites
he authors declare that there is no conlict of interest.
CONFLICT OF INTEREST
After the use of antagonists of alpha-1 and alpha-2 receptors (cimetidine 300mg IV and dexchlorpheniramine 10ml oral route and hydrocortisone 500mg IV), according to snake bite degree (e.g., light snake bite = two lasks of SATL or four to six ampoulesof SAMBL; moderate snake bite = four lasks of SATL or eight to twelve ampoulesof SAMBL), the antivenom injection was done under medical supervision to permit the detection of adverse efects, in accordance to the objective of this study. he snake bite victims were hospitalized for a period of 24h or more. Ater this, if there were no complications to justify further coninement in the hospital, the victim was sent home with instructions to return on the seventh day and ater the iteenth day ater the snake bite. On those occasions, they were evaluated for delayed adverse efects. he quantitative and qualitative registers of detected efects were presented by graphs of comparative analysis between the SATL and the SAMBL (Figure 1).
The distribution of snake bite victims according by characteristic of antivenom was 57% (58/102) to SATL and 43% (44/102) to SAMBL, the ratio of patients were equals (0.5) to both groups of patients, SATL (p-value=0.09, CI=95%) and SAMBL (p-value=0.9, CI=95%).
When the adverse efects between the antivenoms are compared, there are 17% (n=58) of persons with adverse efects with the SATL and 25% (n=44) with the SAMBL (p-value=0.47, CI=99%), the ratio of adverse efects is equal to both in statistic analysis. Although the total number of evaluated victims is only 102 persons, it is possible to say that to this moment (Project Phase II) and in these cases, that the SATL is as safe as SAMBL because had no statistic diference in number of adverse efects between the two antivenoms, as described in Figure 2 . he more frequent adverse efects with the SATL were urticaria, pruritus, facial rubor and vomiting; with the SAMBL the more frequent adverse efects were pruritus, urticaria, vomiting and headache (Figure 1). In according of literature10-12, the adverse efects presented
in this study were expected to occur and could be controlled with other medicines, as soon as they appeared. It was not reason to stop the treatment with both antivenoms (SATL and SAMBL). To urticaria it was 31.3% with SATL and 30.8%
ur�caria pruritus facial rubor vomit nausea hypotension dyspnea angioedema tremor nasal conges�on conjunc�val hyperemia general hyperemia pharyngeal irrita�on 10 8 3 2 1 1 1 1 1 1 1 1 1 4 5 2 1 1 SAMBL SATL
FIGURE 1 - Distribution of adverse efects by type of antivenom (SAMBL and SATL). SAMBL: liquid bivalent and monovalent antivenom serum; SATL: liofilizated trivalent antivenom serum. 30,8 38,5 30,8 31,3 25,0 43,8 Urcaria Pruritus Others % A d v e r s e E ff e c t s SATL SAMBL
FIGURE 2- Distribution of urticaria, pruritus and others adverse effects by type of antivenom (SAMBL and SATL).
SAMBL: liquid bivalent and monovalent antivenom serum; SATL: lioilized trivalent antivenom serum; NS: no signiicance
with SAMBL (p-value=1), to pruritus it was 25% with SATL and 38.5% with SAMBL (p-value=0.58) and to others adverse efects it was 43.8% to SATL and 30.8% to SAMBL (p-value=0.63), there was no statistic signiicance between the two, although there was good tolerance to both antivenoms (Figure 2).
here were no more adverse efects in the SATL, whichwas made with three diferent immunoglobulins, in agreement with the experiences in India13. We believed that this antivenom can be used
when the genus of snake is not known. In the economic aspect, it is clear that the SATL is beter than the SAMBL, as it could be used until eight years, eleven months and seven days ater fabrication, ater revalidation of the study. he SATL was safe for the Bothrops
snake bite. he epidemiological, clinical and therapeutic aspects were studied, and the SATL is viable with priority to the regions where access is diicult due to the long distances from the public health unit. Every patient who used the SATL went home without complications and as evaluated until 15 days ater the speciic therapy. here was
no diference in the safety between both antivenoms (SATL and SAMBL). It is necessary to make the SATL in Brazil because it is more economic for the government and is beter to the people living long distances from the public health unit. he SATL was used for almost nine years ater its production and the SAMBL used until three years ater the eicacy was determined.
he principal objective is to the Amazon Region, where there are important epidemiological characteristics, such as when the public health unit is far from the primary forest and agriculture regions, when there is no electric power to conserve the liquid antivenom in cold temperatures (20C to 80C), and because there are the three genera of
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Rev Soc Bras Med Trop 45(4):523-525, Jul-Aug, 2012FINANCIAL SUPPORT
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